Figure 3.

Effects of SU086 in prostate cancer growth in xenograft models in vivo

(A) Plasma liver enzyme panel was performed on mice treated with SU086 or vehicle control (three mice per condition) for 24 days at indicated dose of 50 mg/kg ip daily. Liver enzymes tested include aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total bilirubin. Samples are charted as average of units/liter (U/L) ± SEM. Statistical analysis: p values were calculated with Student’s t test using the U/L data. Samples were further charted over the upper limit of normal for mice (ULN) by dividing by the following values: AST (388U/L), ALT (160U/L), ALP (183U/L). GGT and bilirubin are not often expressed in normal samples and therefore do not have a ULN value.

(B and C) C4-2 (B) or DU145 (C) xenografts were established in NSG male mice by implanting 5 × 10⁵ cells subcutaneously (s.c.) in 50 μL of Matrigel. Treatment with SU086 (50 mg/kg i.p. daily) or vehicle control was initiated when average tumor volume reached 30–40 mm³ on average. Animal weights and tumor volumes (L × W × H/2) were measured every third day. Tumors were graphed as fold change over respective day 0 volumes ± SEM (C4-2: DMSO n = 10, SU086 n = 9; DU145: DMSO n = 10, SU086 n = 8). Animals were sacrificed when the average tumor volumes of the vehicle-treated group reached 400 mm³ (C4-2) or 500 mm³ (DU145). Tumors collected at the end of the indicated treatments were stained with H&E and an antibody against Ki67. The Ki67 proliferative index was quantified as percentage of positive nuclei per field, as an average of three fields, ±SD. Scale bars indicate 25 μm. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗∗p < 0.001 determined by Student’s t test.